Phase 1 cytotoxic factors
Phase 1 cytotoxic factors MSC462
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This 5 page One Day of Notes was uploaded by Zack Bauman on Monday February 2, 2015. The One Day of Notes belongs to MSC462 at University of Miami taught by Dr. Liza Merly in Fall. Since its upload, it has received 153 views. For similar materials see Marine Biomedicine in Marine Science at University of Miami.
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Date Created: 02/02/15
Chitins etc 22515 The immune system An antigen causes an immune response Diseasecausing antigens are called pathogens The immune system is designed to protect the body from pathogens Immunoadjuvant Substance that nonspeci cally enhances the immune response to an antigen Making the immune system stronger and faster Antigen is any substance usually a foreign body or a component of that body such as a bacterium or virus that binds speci cally to antibody or Tcell receptor Freund s adjuvant Vaccines and adjuvants Many vaccines consist used today consist of o Mainly killed viruses 0 Microbial agents 0 Viral subunits 0 Bacterial toxoids Desired immune response to vaccines 0 Production of antibodies andor generation of cytotoxic T cells Enhanced by adding certain substances to vaccines Previously used vaccines made from livekilled whole organisms were effective but suffered from high reactogenicity As manufacturers developed safer less reactogenic subunit vaccines they found that 0 Lower reactogenicity l reduced vaccine effectiveness Adjuvants 0 Vaccine additives that enhance the elicited levels of antibodies and speci c T lymphocytes Highly heterogeneous Mode of action is formation of an antigen depot with slow release at site of inoculation Followed by presentation of antigen to immunocompetent cells and production of cytokines In conventional vaccines adjuvants are used to elicit an early high and longlasting immune response Newly developed puri ed subunit or synthetic vaccines using biosynthetic or recombinant technologies are poor immunogens Require adjuvants to evoke immune e response Most common adjuvants Aluminum hydroxide aluminum phosphate and calcium phosphate 0 Other adjuvants based on oil emulsions products from bacteria endotoxins and vegetable oils 0 Aluminum widely used in human vaccines for 70 years 0 Molecular MOA unknown Desire for new and improved adjuvants from need to make existing inactivated vaccines more potent Bene ts of incorporating any adjuvant into vaccines must be balanced against any increased reactogenicity or risk of adverse reactions Desired features in adjuvants o Antigen spreading ability More rapid seroprotection Stimulation of Tcell immunity Longer last protective immunity Safety and tolerability Herd immunity everyone vaccinated eradicates pathogen 0 Freund39s adjuvant CFA 0 While it remains the gold standard in terms of adjuvant potency its extreme reactogenicity and toxicity precludes its use in human vaccines 0 Used routinely in labs to promote immune responses production of antibodies lmmunoadjuvant Various forms of chitin may act as immunoadjuvants lmmune reactions to components of exoskeleton of crustaceans carefully studied 0 Lead to recognition Allergic responses to crustaceans Presumed relationship between allergy and presence of chitin investigated 0 In vivo chitin is part of complex structures with other organic and inorganic compounds 0 ln arthropods chitin is covalently linked to proteins and tanned by quinones o Quinone molecule that interacts and adds color lsolated puri ed chitin exerts several bene cial actions 0 Stimulate macrophages by interacting with receptors on the macrophage surface that mediate the internalization of chitin particles to be degraded by lysozyme and NacetylB glucosaminidase Macrophages produce cytokines and other compounds 0 Nonspeci c host resistance against bacterial and viral infections OOOO Immunologic activities of chitin 22715 Immunologic activity of chitin Strong Th1 adjuvant Capable of downregulating Th2 Allergy concerns regarding the use of chitins and other derivatives Many studies investigating potential problems associated with chitins and their derivatives due to shell sh allergy Potent allergen for most shell sh allergies is tropomysin shell sh esh Chitin of marine origin Several different forms 0 Most commonly available from shing activities are from crustaceans o Squids Substantially differ from each other in terms of crystallinity 0 Alpha form vs Beta form squid Exploitation of the chitin resources derived from industrial production of canned or frozen crustaceans These medical grade chemicals are further modi ed in many ways in order to optimize their performances No instrumental analytical technique can identify the raw material from which a given sample of isolated chitin has been produced Other marine adjuvants Killed viral vaccines and bacterial toxoids are weakly immunogenic Numerous compounds are under evaluation as immunological adjuvants and peptidecarriers to improve the immune response Hemocyanins o Multigene family of giant extracellular carrier proteins 0 Serve as oxygen carriers in the blood of many mollusks 0 Copper proteins as opposed to hemoglobin with iron Binds to amino acid side chain Large molecular size Xenogenic character High carbohydrate content Induce strong immune response in mammals AppHed Hapten carriers Adjuvants in immunocompetent tests Experimental antigens in studies of the immune system 0 Isolated from the hemolymph of the animal OOOOO o Oxygenated molecule generates characteristic light absorbance in near UV region blue 0 Megathura crenulata Keyhole limpet Harvest hemocyanin and its immunogenicity Being developed 0 Rapana thomasiana Asian whelk Large predatory snail Hemocyanin present lmmunostimulation Hemocyanins could be used in conjugate vaccines wherein tumor or disease speci c antigens are covalently bound to carrier protein 0 Two forms of stimulation 0 Nonspeci c immunostimulation NSI 0 Active speci c immunostimulation ASI Sharks as source of various immunogenic substances Shark immune cell derived factors 0 Condition cell medium in shortterm cultures contain bioactive factors